Nanocarriers in Tuberculosis Treatment: Challenges and Delivery Strategies.

The World Health Organization identifies tuberculosis (TB), caused by Mycobacterium tuberculosis, as a leading infectious killer. Although conventional treatments for TB exist, they come with challenges such as a heavy pill regimen, prolonged treatment duration, and a strict schedule, leading to multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The rise of MDR strains endangers future TB control. Despite these concerns, the hunt for an efficient treatment continues. One breakthrough has been the use of nanotechnology in medicines, presenting a novel approach for TB treatment. Nanocarriers, such as lipid nanoparticles, nanosuspensions, liposomes, and polymeric micelles, facilitate targeted delivery of anti-TB drugs. The benefits of nanocarriers include reduced drug doses, fewer side effects, improved drug solubility, better bioavailability, and improved patient compliance, speeding up recovery. Additionally, nanocarriers can be made even more targeted by linking them with ligands such as mannose or hyaluronic acid. This review explores these innovative TB treatments, including studies on nanocarriers containing anti-TB drugs and related patents.

Advances in Pancreatic Cancer Treatment by Nano-Based Drug Delivery Systems.

Pancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.

Solid Lipid Nanoparticles vs. Nanostructured Lipid Carriers: A Comparative Review.

Solid-lipid nanoparticles and nanostructured lipid carriers are delivery systems for the delivery of drugs and other bioactives used in diagnosis, therapy, and treatment procedures. These nanocarriers may enhance the solubility and permeability of drugs, increase their bioavailability, and extend the residence time in the body, combining low toxicity with a targeted delivery. Nanostructured lipid carriers are the second generation of lipid nanoparticles differing from solid lipid nanoparticles in their composition matrix. The use of a liquid lipid together with a solid lipid in nanostructured lipid carrier allows it to load a higher amount of drug, enhance drug release properties, and increase its stability. Therefore, a direct comparison between solid lipid nanoparticles and nanostructured lipid carriers is needed. This review aims to describe solid lipid nanoparticles and nanostructured lipid carriers as drug delivery systems, comparing both, while systematically elucidating their production methodologies, physicochemical characterization, and in vitro and in vivo performance. In addition, the toxicity concerns of these systems are focused on.

The Impact of Flavonoid-Loaded Nanoparticles in the UV Protection and Safety Profile of Topical Sunscreens.

Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings.

Pluronic® triblock copolymer-based nanoformulations for cancer therapy: A 10-year overview.

This paper provides a review of the literature on the use of Pluronic® triblock copolymers for drug encapsulation over the last 10 years. A special focus is given to the progress of drug delivery systems (e.g., micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic® triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to innovative examples for improving tumor cytotoxicity while reducing side effects.

Chitosan Nanoparticles: A Versatile Platform for Biomedical Applications.

Chitosan is a biodegradable and biocompatible natural polymer that has been extensively explored in recent decades. The Food and Drug Administration has approved chitosan for wound treatment and nutritional use. Furthermore, chitosan has paved the way for advancements in different biomedical applications including as a nanocarrier and tissue-engineering scaffold. Its antibacterial, antioxidant, and haemostatic properties make it an excellent option for wound dressings. Because of its hydrophilic nature, chitosan is an ideal starting material for biocompatible and biodegradable hydrogels. To suit specific application demands, chitosan can be combined with fillers, such as hydroxyapatite, to modify the mechanical characteristics of pH-sensitive hydrogels. Furthermore, the cationic characteristics of chitosan have made it a popular choice for gene delivery and cancer therapy. Thus, the use of chitosan nanoparticles in developing novel drug delivery systems has received special attention. This review aims to provide an overview of chitosan-based nanoparticles, focusing on their versatile properties and different applications in biomedical sciences and engineering.

Microfluidic production of mRNA-loaded lipid nanoparticles for vaccine applications.

INTRODUCTION: During past years, lipid nanoparticles (LNPs) have emerged as promising carriers for RNA delivery, with several clinical trials focusing on both infectious diseases and cancer. More recently, the success of messenger RNA (mRNA) vaccines for the treatment of severe diseases, such as acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partially justified by the development of LNPs encapsulating mRNA for efficient cytosolic delivery. AREAS COVERED: This review examines the production and formulation of LNPs by using microfluidic devices, the status of mRNA-loaded LNPs therapeutics and explores spray drying process, as a promising dehydration process to enhance LNP stability and provide alternative administration routes. EXPERT OPINION: Microfluidic techniques for preparation of LNPs based on organic solvent injection method promotes the generation of stable, uniform, and monodispersed nanoparticles enabling higher encapsulation efficiency. In particular, the application of microfluidics for the fabrication of mRNA-loaded LNPs is based on rapid mixing of small volumes of ethanol solution containing lipids and aqueous solution containing mRNA. Control of operating parameters and formulation has enabled the optimization of nanoparticle physicochemical characteristics and encapsulation efficiency.

Enhanced Anticancer Activity of Hymenocardia acida Stem Bark Extract Loaded into PLGA Nanoparticles.

Hymenocardia acida (H. acida) is an African well-known shrub recognized for numerous medicinal properties, including its cancer management potential. The advent of nanotechnology in delivering bioactive medicinal plant extract with poor solubility has improved the drug delivery system, for a better therapeutic value of several drugs from natural origins. This study aimed to evaluate the anticancer properties of H. acida using human lung (H460), breast (MCF-7), and colon (HCT 116) cancer cell lines as well as the production, characterization, and cytotoxicity study of H. acida loaded into PLGA nanoparticles. Benchtop models of Saccharomyces cerevisiae and Raniceps ranninus were used for preliminary toxicity evaluation. Notable cytotoxic activity in benchtop models and human cancer cell lines was observed for H. acida crude extract. The PLGA nanoparticles loading H. acida had a size of about 200 nm and an association efficiency of above 60%, making them suitable to be delivered by different routes. The outcomes from this research showed that H. acida has anticancer activity as claimed from an ethnomedical point of view; however, a loss in activity was noted upon encapsulation, due to the sustained release of the drug.

Insights into Nanomedicine for Head and Neck Cancer Diagnosis and Treatment.

Head and neck cancers rank sixth among the most common cancers today, and the survival rate has remained virtually unchanged over the past 25 years, due to late diagnosis and ineffective treatments. They have two main risk factors, tobacco and alcohol, and human papillomavirus infection is a secondary risk factor. These cancers affect areas of the body that are fundamental for the five senses. Therefore, it is necessary to treat them effectively and non-invasively as early as possible, in order to do not compromise vital functions, which is not always possible with conventional treatments (chemotherapy or radiotherapy). In this sense, nanomedicine plays a key role in the treatment and diagnosis of head and neck cancers. Nanomedicine involves using nanocarriers to deliver drugs to sites of action and reducing the necessary doses and possible side effects. The main purpose of this review is to give an overview of the applications of nanocarrier systems to the diagnosis and treatment of head and neck cancer. Herein, several types of delivery strategies, radiation enhancement, inside-out hyperthermia, and theragnostic approaches are addressed.

Fusions of a carbohydrate binding module with the small cationic hexapeptide RWRWRW confer antimicrobial properties to cellulose-based materials.

The emergence of antibiotic-resistant bacteria is a critical worldwide healthcare problem. In the specific case of wound care, new and effective alternatives to currently available solutions are urgently needed. Cellulose-based dressings, for example, could be made more attractive if rendered antimicrobial. This work proposes a new strategy to modify cellulose-based materials with the short antimicrobial hexapeptide MP196 (RWRWRW-NH2) that relies on a biomolecular recognition approach based on carbohydrate binding modules (CBMs). Specifically, we focused on the modification of hydrogels, paper, and microfibrillated cellulose (MFC) with fusions of the CBM3 from Clostridium thermocellum (C. thermocellum) with derivatives of MP196. The fusions are prepared by promoting the formation of a disulfide bond between Cys-terminated derivatives of MP196 and a CBM3 that is pre-anchored in the materials. The CBM3-MP196-modified materials displayed antibacterial activity against Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) that was significantly higher when compared with the activity of materials prepared by physical adsorption of MP196. The biomolecular strategy provides a more favorable orientation, exposure, and distancing of the peptide from the matrix. This versatile concept provides a toolbox for the functionalization of cellulose materials of different origins and architectures with a broad choice in peptides. Functionalization under mild biological conditions avoids further purification steps, allowing for translational research and multiple applications as drug delivery systems, scaffolds for tissue engineering and biomaterials. STATEMENT OF SIGNIFICANCE: The emergence of antibiotic-resistant bacteria is a critical worldwide healthcare problem. In the specific case of wound care, new and effective alternatives to currently available solutions are urgently needed. This work proposes a new strategy to modify cellulose-based materials with a short antimicrobial hexapeptide that relies on a biomolecular recognition approach based on carbohydrate binding modules. The modified materials displayed antibacterial activity against both Gram-negative and Gram-positive bacteria. The biomolecular strategy provides a favorable orientation, exposure, and distancing of the peptide from the matrix. This versatile concept offers a toolbox for the functionalization of different cellulose materials with a broad choice in peptides. Functionalization under mild biological conditions avoids further purification steps, allowing for translational research and multiple applications.

Evaluation of the Antitumour and Antiproliferative Effect of Xanthohumol-Loaded PLGA Nanoparticles on Melanoma.

Cutaneous melanoma is the deadliest type of skin cancer and current treatment is still inadequate, with low patient survival rates. The polyphenol xanthohumol has been shown to inhibit tumourigenesis and metastasization, however its physicochemical properties restrict its application. In this work, we developed PLGA nanoparticles encapsulating xanthohumol and tested its antiproliferative, antitumour, and migration effect on B16F10, malignant cutaneous melanoma, and RAW 264.7, macrophagic, mouse cell lines. PLGA nanoparticles had a size of 312 ± 41 nm and a PdI of 0.259, while achieving a xanthohumol loading of about 90%. The viability study showed similar cytoxicity between the xanthohumol and xanthohumol-loaded PLGA nanoparticles at 48 h with the IC50 established at 10 µM. Similar antimigration effects were observed for free and the encapsulated xanthohumol. It was also observed that the M1 antitumor phenotype was stimulated on macrophages. The ultimate anti-melanoma effect emerges from an association between the viability, migration and macrophagic phenotype modulation. These results display the remarkable antitumour effect of the xanthohumol-loaded PLGA nanoparticles and are the first advance towards the application of a nanoformulation to deliver xanthohumol to reduce adverse effects by currently employed chemotherapeutics.

Systematic Review of the Application of Perinatal Derivatives in Animal Models on Cutaneous Wound Healing.

Knowledge of the beneficial effects of perinatal derivatives (PnD) in wound healing goes back to the early 1900s when the human fetal amniotic membrane served as a biological dressing to treat burns and skin ulcerations. Since the twenty-first century, isolated cells from perinatal tissues and their secretomes have gained increasing scientific interest, as they can be obtained non-invasively, have anti-inflammatory, anti-cancer, and anti-fibrotic characteristics, and are immunologically tolerated in vivo. Many studies that apply PnD in pre-clinical cutaneous wound healing models show large variations in the choice of the animal species (e.g., large animals, rodents), the choice of diabetic or non-diabetic animals, the type of injury (full-thickness wounds, burns, radiation-induced wounds, skin flaps), the source and type of PnD (placenta, umbilical cord, fetal membranes, cells, secretomes, tissue extracts), the method of administration (topical application, intradermal/subcutaneous injection, intravenous or intraperitoneal injection, subcutaneous implantation), and the type of delivery systems (e.g., hydrogels, synthetic or natural biomaterials as carriers for transplanted cells, extracts or secretomes). This review provides a comprehensive and integrative overview of the application of PnD in wound healing to assess its efficacy in preclinical animal models. We highlight the advantages and limitations of the most commonly used animal models and evaluate the impact of the type of PnD, the route of administration, and the dose of cells/secretome application in correlation with the wound healing outcome. This review is a collaborative effort from the COST SPRINT Action (CA17116), which broadly aims at approaching consensus for different aspects of PnD research, such as providing inputs for future standards for the preclinical application of PnD in wound healing.

Nanocarrier-Mediated Topical Insulin Delivery for Wound Healing.

Wound care has been clinically demanding due to inefficacious treatment that represents an economic burden for healthcare systems. In Europe, approximately 7 million people are diagnosed with untreated wounds, leading to a cost between 6.000€ and 10.000€ per patient/year. In the United States of America, 1.5 million people over 65 years old suffer from chronic wounds. A promising therapeutic strategy is the use of exogenous growth factors because they are decreased at the wound site, limiting the recovery of the skin. Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. The aim of this review is to perform a standing point about a promising strategy to treat different types of wounds by the topical delivery of insulin-loaded nanocarriers.

Intranasal drug delivery for treatment of Alzheimer's disease.

The Alzheimer's disease is a neurodegenerative condition with severe consequences interfering with patient quality of life. It is characterized as a progressive and irreversible brain disorder hampering memory and thinking, affecting the capacity to perform daily tasks leading to physical and cognitive incapacitation. The conventional treatment occurs by the oral route, but it presents relevant drawbacks such as low bioavailability, fast metabolism, limited brain exposure, and undesirable side effects. The intranasal route has been proposed as a promising alternative to deliver drugs and improve the Alzheimer's disease treatment. Still, there is not a clear alternative delivery system available in the market with advantageous bioavailability and safety. The aim of this review is to perform an overview on the strategies for drug intranasal delivery for Alzheimer's disease treatment. The advantages and disadvantages of this delivery route and the delivery systems developed so far are discussed. A special focus is given on the use of permeation enhancers, the types of intranasal drug delivery devices, as well as possible toxicity concerns.

An Overview on Spray-Drying of Protein-Loaded Polymeric Nanoparticles for Dry Powder Inhalation.

The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.

Design and synthesis of novel quinic acid derivatives: in vitro cytotoxicity and anticancer effect on glioblastoma.

Aim: Quinic acid (QA) is a cyclic polyol exhibiting anticancer properties on several cancers. However, potential role of QA derivatives against glioblastoma is not well established. Methodology & results: Sixteen novel QA derivatives and QA-16 encapsulated poly (lactic-co-glycolic acid) nanoparticles (QA-16-NPs) were screened for their anti-glioblastoma effect using standard cell and molecular biology methods. Presence of a tertiary hydroxy and silylether groups in the lead compound were identified for the antitumor activity. QA-16 have 90% inhibition with the IC50 of 10.66 µM and 28.22 µM for LN229 and SNB19, respectively. The induction of apoptosis is faster with the increased fold change of caspase 3/7 and reactive oxygen species. Conclusion: QA-16 and QA-16-NPs shows similar cytotoxicity effect, providing the opportunity to use QA-16 as a potential chemotherapeutic agent.

Unravelling the Immunotoxicity of Polycaprolactone Nanoparticles-Effects of Polymer Molecular Weight, Hydrolysis, and Blends.

Poly-ε-caprolactone (PCL) is a biodegradable polyester that has FDA and CE approval as a medical device. Nonetheless, the lack of toxicity exhibited by the polymer cannot be extrapolated to its nanomaterial conformation. Despite PCL-based NPs being widely studied in the biomedical field for their advantages as controlled drug delivery systems, little data describe PCL NPs' toxicity, particularly immunotoxicity. This work assessed different PCL-based delivery systems intended for protein delivery regarding their immunotoxicity and hemocompatibility. Two different molecular weight PCL polymers were used, as well as blends with chitosan and glucan. Results showed that the presence of NaOH during the production of PCL2 NPs and PCL2/glucan NPs induced PCL alkali hydrolysis, generating more reactive groups (carboxyl and hydroxyl) that contributed to an increased toxicity of the NPs (higher reduction in peripheral blood mononuclear cell viability and lower hemocompatibility). PCL2/glucan NPs showed an anti-inflammatory activity characterized by the inhibition of LPS stimulated nitric oxide (NO) and TNF-α. In conclusion, generalizations among different PCL NP delivery systems must be avoided, and immunotoxicity assessments should be performed in the early stage of product development to increase the clinical success of the nanomedicine.

Is an Early Diagnosis of COPD Clinically Useful? / ¿Es clínicamente útil un diagnóstico temprano de EPOC?

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Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells.

The renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50 µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin's solubility/loading while allowing the maintenance of rutin's anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs-nanoparticles hybrid systems, allowing controlled drug delivery.

Novel and revisited approaches in nanoparticle systems for buccal drug delivery.

The buccal route is considered patient friendly due to its non-invasive nature and ease of administration. Such delivery route has been used as an alternative for the delivery of drugs that undergo first-pass metabolism or are susceptible to pH and enzymatic degradation, such as occurs in the gastrointestinal tract. However, the drug concentration absorbed in the buccal mucosa is often low to obtain an acceptable therapeutic effect, mainly due to the saliva turnover, tongue and masticatory movements, phonation, enzymatic degradation and lack of epithelium permeation. Therefore, the encapsulation of drugs into nanoparticles is an important strategy to avoid such problems and improve their buccal delivery. Different materials from lipids to natural or synthetic polymers and others have been used to protect and deliver drugs in a sustained, controlled or targeted manner, and enhance their uptake through the buccal mucosa improving their bioavailability and therapeutic outcome. Overall, the main aim of this review is to perform an overview about the nanotechnological approaches developed so far to improve the buccal delivery of drugs. Herein, several types of nanoparticles and delivery strategies are addressed, and a special focus on pipeline products is also given.